Impact of COVID-19 pandemic on ocular disease: KNHANES 2015–2021

The aim of this study was to evaluate the impact of COVID-19 on ocular diseases and changes in risk factors before and after the COVID-19 pandemic. This study was conducted using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2015–2021, a national cross-sectional health examination and survey. Associations between ocular diseases and risk factors were determined using the chi-squared test and logistic regression analysis. Bivariable adjusted logistic regression analysis was performed to examine the odds ratio (OR) and 95% confidence interval (CI) to evaluate of the impact of COVID-19 on ocular diseases. Individuals were divided into two age groups (< 60 and ≥ 60 years). A total of 50,158 people were diagnosed, of whom 7270 were diagnosed with cataract, 921 with glaucoma, and 439 with age-related macular degeneration (AMD). Risk factors for cataract were COVID-19 pandemic (OR 1.161), hypertension (OR 1.608), diabetes (OR 1.573), dyslipidemia (OR 1.167), stroke (OR 1.272), and depression (OR 1.567). Risk factors for AMD were COVID-19 pandemic (OR 1.600), dyslipidemia (OR 1.610), and depression (OR 1.466). Risk factors for glaucoma were hypertension (OR 1.234), dyslipidemia (OR 1.529), diabetes (OR 1.323), and depression (OR 1.830). The COVID-19 pandemic was a risk factor for cataracts and AMD, but not for glaucoma. Cataracts and AMD may be more influenced by the acquired health conditions or the environment.

For this cross-sectional, population-based study, we used data from the KNHANES 2015-2021, a series of cross-sectional surveys of nationally representative samples of the Korean civilian population, conducted annually to assess the health and nutrition status of the South Korean population.To obtain representative samples, KNHANES uses a stratified, multistage, cluster probability sampling design by geographical area, age, and sex.For the health interview survey, a trained interviewer asked questions directly to individuals aged ≥ 19 years old.The inclusion criteria for this study were: (1) adults over 19 years of age, (2) those who completed a questionnaire on independent risk factors.Our exclusion criteria were aged < 19 years.Subjects were asked whether they had been diagnosed with cataracts by an ophthalmologist, in the same way as they were asked whether they had been diagnosed with cataract, glaucoma or AMD.Risk factors such as diabetes, hypertension, dyslipidemia, major depression disorder (MDD), and aerobic physical activity were questioned.Incorrect or untested responses (untested) were excluded (Fig. 1).The population was divided according to age: young (< 60 years) or older (≥ 60 years).The pre-COVID-19 period was 2015-2019, and the post-COVID-19 period was set at 2020-2021.
Statistical analyses were performed using SPSS Version 27.0 (SPSS Inc., IBM Software, Portsmouth, UK), and two-tailed p-values less than 0.05 were considered statistically significant.To estimate the odds ratios (ORs) of cataract and potential factors, we performed binary logistic regression analyses using a generalized linear model for a complex survey design.The ORs measure the odds of an outcome occurring in the presence of various risk factors compared to the odds of the outcome occurring in their absence.ORs are presented with corresponding 95% confidence intervals (CIs).CIs provide a range of values that are believed to cover the true value of the ORs to a 95% level of confidence, thus giving an indication of the precision of our estimates.

Institutional review board statement
This study was approved by the Institutional Review Board of Kangnam Sacred Heart Hospital (Approval number: 2024-04-009).

Results
The characteristics of the study population are shown in     2 and Fig. 2A).Aerobic physical activity was the protective factor (OR 0.820; 95% CI 0.769-0.874).Before the COVID-19 pandemic, risk factors for cataract were sex (OR 1.437; 95% CI  2 and Fig. 2B).Aerobic physical activity was a protective factor (OR 0.837; 95% CI 0.772-0.909).However, stroke and personal income was not significant factor.After the start of the COVID-19 pandemic, stroke (OR 1.700; 95% CI 1.346-2.147)was found to be an important risk factor in addition to existing risk factors and middle-lower income to be a protective factor (Table 2 and Fig. 2C).

Discussion
The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, emerged in late 2019 and rapidly evolved into a global health crisis 9 .It has led to widespread disease and significant mortality, with a profound impact on public health, economies, and daily life worldwide 9 .In this study, we investigated the effect of the COVID-19 pandemic on the prevalence and risk factors for ocular disease.This study found that COVID-19 pandemic was an important risk factor for cataract and AMD, but not for glaucoma.There may be several possible reasons why the prevalence of cataract and AMD has increased since the COVID-19 outbreak.First, changes in diet and lifestyle due to the COVID-19 pandemic.Changes in lifestyle due to the pandemic may affect nutritional status and daily activities, which may also affect the risk factors for ocular diseases such as diabetes, dyslipidemia and hypertension due to restrictions on outdoor activities 10 .Second, with immune system changes, COVID-19 affects the patient's immune system.This may worsen existing eye diseases or increase the risk of developing new eye diseases.COVID-19 causes epigenetic changes and hyperactivation in monocytes and permanent changes in stem cell gene expression, causing the immune system to produce more white blood cells 11 .The third is the postponement or cancellation of regular eye examinations due to COVID-19.Many people have been unable to access regular health care during the pandemic, including the postponement or cancellation of eye examinations.This may have the delayed early detection and treatment of some eye diseases.Fourth, social isolation and stress: prolonged social isolation can have a negative impact on mental health, which can also affect physical health, especially eye health.Stress is known to be a risk factor for several eye diseases 12 .In addition, with many people spending more time at home due to social isolation, screen time on computers, smartphones and other devices has increased.This can lead to increased vision problems and eye fatigue 13 .Furthermore, oxidative stress, which is a main pathogenesis of cataract and AMD, is increased by COVID-19 infection and damages the lens and retinal pigment epithelium 14,15 .However, the COVID-19 pandemic is not a risk factor for glaucoma.Glaucoma is thought to be caused more by endogenous factors rather than exogenous factors.COVID-19 is caused by the SARS-CoV-2 virus, which primarily affects the respiratory system but can also impact other organs due to its inflammatory and vascular effects 16 .Glaucoma, on the other hand, is a group of eye conditions that primarily involve the degeneration of the optic nerve, often associated with increased intraocular pressure 17 .The etiology of glaucoma is complex, involving genetic, vascular, and mechanical components that are not directly influenced by viral infections like COVID-19 17 .
This study showed that risk factors have changed since the COVID-19 pandemic.Stroke was not a risk factor for cataract, but after the COVID-19 pandemic, it became an important risk factor.In AMD, dyslipidemia was a major risk factor rather than sex, but this was reversed after the COVID-19 pandemic.These changes in risk factors may be due to changes in the immune system caused by coronavirus infection.COVID-19 may trigger stronger inflammatory responses in men 18,19 .Glaucoma was not associated with diabetes and aerobic physical activity before the COVID-19 pandemic, but became associated after the COVID-19 pandemic.Lifestyle factors may become important in the management and reduction of glaucoma risk factors.Surprisingly, household income had an effect on the change of risk factors.For cataracts, income was not a risk factor in pre-COVID-19, but upper-middle income was a protective factor for low income in post-COVID-19.For AMD, income was not a risk factor in pre-COVID-19, but an increase in income was a risk factor for low income in post-COVID-19.This is likely to have been influenced by the increase in home offices, long-time computer use, decline in outdoor physical activities, and social isolation among the upper-middle income class post-COVID-19 during the pandemic.
In conclusion, the COVID-19 pandemic was a risk factor for cataract and AMD, but not for glaucoma.Cataract and AMD may be more affected by the external factors than glaucoma.The indirect effects of the pandemic, such as stress, changes in immune system, changes in access to healthcare, and lifestyle changes, are likely to play a significant role in these observed trends.

Fig. 2 .
Fig. 2. Forest plots showing the odds ratio with 95% confidence interval.(A-C) The association between cataracts and risk factors in total study periods, pre-COVID-19 and post-COVID-19.(D-F) The association between AMD and risk factors in total study periods, pre-COVID-19 and post-COVID-19.(G-I) The association between glaucoma and risk factors in total study periods, pre-COVID-19 and post-COVID-19.

Table
. Of the 61,567 people in KHANES 2015-2021, 50,158 people (22,284 men and 27,874 women) over 19 years of age were included in this study, excluding 11,409 under 19 years of age.Of these, 33,073 were pre-COVID-19 and 17,085 were post-COVID-19.Of these, 7270 were diagnosed with cataracts, 921 with glaucoma and 439 with AMD.Mean age was 51.88 ± 17.09 years.Disease prevalence by year is shown in Table1 and